Forum for Science, Industry and Business

How fish mend a broken heart

03.11.2006

New evidence to explain how a common tropical fish mends a broken heart may suggest methods for coaxing the damaged hearts of mammals to better heal, researchers report in the November 3, 2006 issue of Cell, published by Cell Press.

The researchers found that the hearts of zebrafish harbor progenitor cells that spring into action to restore wounded heart muscle. Cells from a membrane layer that surrounds the heart, called the epicardium, follow suit, invading the wounded cardiac tissue and stimulating the growth of new blood vessels.

"Zebrafish can survive pretty massive injury to the heart--the loss of about a quarter of their ventricle," said Kenneth Poss of Duke University Medical Center. The ventricle, which receives blood and then pumps it back out to the body, is one of two chambers that make up the fish heart. "This study gets at some of the important mechanistic questions about how they rebuild the heart, and some of the key factors that contribute."

In contrast to zebrafish, the cardiac damage and scarring caused by heart attacks is a major killer among humans, making "the inability to replace damaged cardiac muscle one of the most prominent regenerative failures of mammals," wrote Alexandra Lepilina and Ashley Coon, the study's first authors.

However, mammalian hearts have been found to contain rare populations of progenitor cells, they added. As in zebrafish, the hearts of adult mammals, including humans, are also housed inside an epicardium, a tissue about which little is known.

"Scientists haven't paid much attention to the epicardium in adults," Poss said. "These findings in fish should encourage more exploration of what adult epicardium can do.

"There is the potential that these cells could be utilized for therapies."

The ability to regenerate tissue is a feature shared among vertebrate species, the researchers said. However, particular animals, including certain amphibians and fish, display an "elevated regenerative spectrum, with many more tissues capable of impressive regeneration," they said. For instance, certain newts or salamanders can regenerate limbs, spinal cord, retina, brain, and heart tissue.

While progenitor cell populations have been identified within most mammalian organs, including skin, skeletal muscle, brain, and heart, these cells vary widely in frequency and the ability to regenerate damaged or lost tissue, they said. In most mammalian organs, progenitor cells can restore cells lost in the course of normal organ function or after minor injury but cannot regenerate after major damage or removal of structures.

"It is believed that the capacity for regeneration is an ancestral condition that has occasionally been lost in the course of vertebrate evolution." Poss said. "Thus, most biologists suspect that the machinery to optimize regeneration from progenitor cells is present, but lies dormant, in mammals."

In an earlier study, Poss and his colleagues found that zebrafish have a unique ability to regenerate cardiac muscle after major injury. They further suspected that illumination of the fishes' ability might offer important insights into "how heart regeneration is naturally optimized."

In the current study, they found that heart regeneration proceeds through two coordinated stages. First, a mass of undifferentiated, pre-cardiac cells form. Those progenitor cells then begin to differentiate and divide, to replace the damaged heart muscle.

In the second step, the epicardium surrounding the heart chambers "lights up" with activity as developmental genes switch on, Poss said. The epicardium expands to rapidly cover the wounded heart muscle.

A subset of those epicardial cells then alters their identity, invading the wound and providing essential new blood vessels to the growing muscle.

They further found that the two-part regeneration process is coordinated by so-called "fibroblast growth factor" (Fgf) signals. Fgf signals are known for their ability to encourage invasive cell behavior, Poss explained.

Indeed, they found, heart muscle cells produce the growth factor, while epicardial cells harbor receptors that are triggered by the signal. When the researchers experimentally blocked the Fgf signal, heart regeneration failed.

"It is tempting to speculate that the ability to mobilize epicardial cells and cultivate such a cardiogenic environment is a primary reason why zebrafish, as opposed to other laboratory models, effectively regenerate [heart muscle]," the researchers concluded. Indeed, they added, mammalian hearts typically show insufficient blood vessel growth after a heart attack.

"Experimental attempts to modify this deficiency are underway, including delivery of growth factors or bone marrow-derived cells that may promote [the formation of new blood vessels]…Success in these pursuits or by directly utilizing epicardial cells or their progenitors could prove favorable for encouraging regeneration from mammalian cardiac progenitor cells."

Die letzten 5 Focus-News des innovations-reports im Überblick:

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...